The purpose of this study has been to determine the value of high dose intensive combination chemotherapy for patients with diffuse histiocytic lymphomas utilizing measures to prevent infection which include laminar air flow isolation and prophylactic oral non-absorbable antibiotics. Patients with stage III and IV diffuse histiocytic lymphoma have been placed in reverse isolation in a laminar air flow unit, have commenced on prophylactic non-absorbable oral antibiotics, and given high dose chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisone. Seven patients have been entered to date and in general, the tolerance to the high doses of chemotherapy have been good. Myelosuppression has generally occured on days 10-14, after the initial administration of agents and, though often severe, has generally been brief. Results to date have been two pathologically confirmed complete responses and two patients who clinically achieved complete remission, but died as a result of sepsis during myelosuppression. There have been two failures on therapy, both patients having died toward the completion of their induction. One patient is currenlty too early for evaluation. The durations of remissions for the two pathologically confirmed complete responses have been 25 plus months and 10 months, the second patient having eventually succumbed to cumulative cardiac toxicity from adriamycin therapy. Although the results of this study suggest that if patients are unable to achieve complete response then long term duration of remission may be good, but the therapy is very aggressive and it still remains to be detemined whether such approaches are justified.